Cancer patients often experience chemotherapy-induced anemia (CIA), a condition that is associated with fatigue and a reduced quality of life. However, CIA can be effectively managed with erythropoiesis-stimulating agents (ESAs) in 50-70% of patients. Research has shown that the concomitant use of iron with ESAs could hold further potential therapeutic benefits, although the use of intravenous (IV) iron administration has not been well explored in CIA patients. A recent study examined whether concomitant IV iron use improved hemoglobin (Hb) level responses in patients treated with darbepoetin alfa.

The 16-week study enrolled 398 CIA patients receiving darbepoetin alfa who were randomized to either an IV iron or a standard practice (oral iron or no iron) group. Patients received 500 μg of darbepoetin alfa and either 200 mg of IV iron or standard practice at 3-week intervals. The primary end point was defined as the proportion of patients achieving a hematopoietic response (Hb  ≥12 g/dL or a ≥2-g/dL increase in Hb levels during the 16-week period). Several secondary end points were also measured, including time to hematopoietic response and the proportion of patients requiring red blood cell (RBC) transfusions.

Of the original cohort, 67% of patients in the IV iron group and 76% in the standard practice group completed the study. The hematopoietic response rates of the IV iron group were significantly higher compared to the control group. In terms of secondary endpoints, the IV iron group also responded more rapidly, and required significantly less RBC transfusions than the control group. Also, the incidence of adverse events, such as nausea, abdominal pain, and more serious cardiovascular and thromboembolic events, were similar in both treatment groups, indicating a favorable benefit-to-risk ratio.

The results of this study point to a wide range of clinical benefits associated with concomitant IV iron administration with ESAs. In addition to a higher hematopoietic response, a reduction in the number of RBC transfusions in CIA patients means lower risks of infection and other immune-related reactions. This study was also the largest trial of its kind, and the authors contend it will provide new options for ESA and iron dosing schedules. Although the results may not be generalizable to all CIA patients, more work is needed to determine which subsets of these patients will benefit most from this clinical technique, concluded the authors.

Bastit L, Vandebroek A, Altintas S, Gaede B, Pintér T, Suto TS, Mossman TW, Smith KE, Vansteenkiste JF. Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. J Clin Oncol. 2008 Apr 1;26(10):1611-8.

NAAC Expert Commentary:
Patients with cancer often experience anemia of inflammation (anemia of chronic disease). Despite adequate iron stores, these patients are unable to mobilize iron for erythropoiesis. Presumably, this is the effect of increased concentrations in the circulation of hepcidin – an enzyme that destroys ferroportin, the protein responsible for iron transport. The administration of iron intravenously may then improve the erythropoietic response to ESAs in cancer patients.

This study by Bastit et al proves this hypothesis and confirms a previous smaller study by Auerbach et al¹. In Bastit, patients treated with 200 mg of IV gluconate or iron sucrose experienced a more rapid and complete response to darbepoetin alpha. Iron-treated patients required a lower number of blood transfusions.

These data are of interest, but not unexpected, and are unable to influence current practice. Given the current guidelines for ESA treatment in cancer, a rapid erythropoietic response may represent an unfavorable event. It is encouraging that anemia management with iron was not associated with increased incidence of deep vein thrombosis, an association that had been feared. While a larger sampling of patients may reveal more differences in complication rates, it is unlikely that those differences may be expected because of a rapid hemoglobin improvement.

In summary, the study confirms the effectiveness of IV iron in patients treated with ESAs and indicates that rapid increases in erythropoietin are not associated with an increased risk of complications. However, the results of this study are unlikely to change current practice until, at a minimum, the safe utilization of ESAs is demonstrated.

Reference

1. Auerbach M, Ballard H, Trout JR, McIlwain M, Ackerman A, Bahrain H, Balan S, Barker L, Rana J. Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial. J Clin Oncol. 2004 Apr 1;22(7):1301-7.

Last Modified: September 4, 2008